Each year millions of Americans suffer from tendon injuries, resulting in impaired work performance and reduction in quality of life while costing billions of healthcare dollars in treatment. Injured tendons heal poorly and form scar tissue, which is prone to re-injury because of its inferior mechanical strength. Current treatments are largely ineffective in restoring normal structure and function to injured tendons. The objective of this project is to enhance the quality of tendon healing by using newly discovered tendon stem cells (TSCs), platelet-rich plasma (PRP), and engineered tendon matrix (ETM). The TSCs, PRP, and ETM will be implanted into tendon window defects on a well-established rabbit injury model. Then, biological and histological properties of the injured tendon at short and long term time points, 6 and 26 weeks, respectively, will be assessed. In addition, the functional recovery of injured tendons will be evaluated by mechanical testing of tendon specimens to determine their structural and mechanical properties. This study is highly innovative in that a potent combination of tendon-specific regenerative cells (TSCs), natural healing growth factors (PRP), and tendon specific matrix components (ETM) will be explored for the first time to enhance tendon repair. The findings of this study may lead to application of this combination therapy clinically to effectively repair or possibly regenerate injured tendons, thus benefiting millions of tendon injury patients in the United States alone. Moreover, we will use the proven tendon injury mode in this study as a stepping-stone for further studying healing problems of other tendon types, including flexor and rotator cuff tendons. PUBLIC HEALTH RELEVANCE: Using a combination of tendon stem cells (TSCs), platelet-rich plasma (PRP), and engineered tendon matrix (ETM), this project aims to enhance repair of acutely injured tendons. The results of this study may lead to a new effective clinical treatment for injured tendons, thus benefiting millions of tendon injury patients in the United States alone. In addition, this study will serve as a stepping-stone for investigating healing problems of other types of injured tendons, including flexor and rotator cuff tendons.